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Peripheral blood γ‐δ T cells lyse fresh human brain—Derived oligodendrocytes
Author(s) -
Freedman Mark S.,
Ruijs Theodora C. G.,
Selin Liisa K.,
Antel Jack P.
Publication year - 1991
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.410300608
Subject(s) - myelin , major histocompatibility complex , multiple sclerosis , oligodendrocyte , biology , t cell , antigen , immunology , myelin basic protein , microbiology and biotechnology , immune system , central nervous system , neuroscience
T cells are postulated to contribute to the injury of the oligodendrocyte‐myelin complex underlying the demyelinating disease multiple sclerosis (MS). The apparent lack of class I or II major histocompatibility complex (MHC) expression in situ on human oligodendrocytes and the consistent failure to identify a universal myelin antigen in MS suggest that the immune damage might be mediated by effector T cells that are capable of reacting in an antigen‐nonspecific and possibly MHC‐unrestricted manner, such as T cells expressing the γ‐δ T‐cell receptor. Since γ‐δ T cells are reported to be present in MS plaques and an increased number are found in the cerebrospinal fluid of patients with MS, we directly examined whether γ‐δ T cells are capable of inducing injury to human oligodendrocytes. We found, using a 6‐hour 51 Cr release assay, that oligodendrocytes cultured from surgically resected human brain specimens were effectively lysed in a dose‐dependent manner by human γ‐δ T Cells (28 ± 5% mean specific lysis, n = 6, at an effector‐target ratio of 20:1). Although heat shock protein HSP72, a putative γ‐δ T‐cell recognition molecule, could be induced in vitro in our oligodendrocytes, an antibody to HSP72 did not inhibit γ‐δ T cell‐mediated lysis of oligodendrocytes. These results suggest that γ‐δ T cells gaining entry into the central nervous system may be deleterious to oligodendrocytes and thus may contribute to the pathogenesis of MS.